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Analysis of the Secondary Structure of Chromatin Linker Proteins HMGB1 and H1 and their Complexes 染色质连接蛋白 HMGB1 和 H1 及其复合物的二级结构分析
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-07 DOI: 10.1134/s0006350923050081
E. V. Chikhirzhina, A. M. Polyanichko

Abstract

The nonhistone chromosomal protein HMGB1 and histone H1 are chromatin linker proteins. The functions of linker proteins are closely related to their conformational state. The structure of proteins that play a key role in the formation of higher levels of chromatin structural organization is being actively studied. In this study, a comparative analysis of the secondary structure of the linker histone H1 and the nonhistone protein HMGB1 was carried out. Using circular dichroism in the UV region and FTIR spectroscopy, it was shown that positively charged histone H1 binds to the C-terminal fragment of HMGB1, stabilizing the resulting complex and inducing the formation of additional α-helical regions in both proteins.

摘要 非组蛋白染色体蛋白HMGB1和组蛋白H1是染色质连接蛋白。连接蛋白的功能与其构象状态密切相关。在染色质高级结构组织形成过程中起关键作用的蛋白质的结构正在被积极研究。本研究对连接蛋白组蛋白 H1 和非组蛋白 HMGB1 的二级结构进行了比较分析。利用紫外区的圆二色性和傅立叶变换红外光谱,研究表明,带正电荷的组蛋白 H1 与 HMGB1 的 C 端片段结合,稳定了由此产生的复合物,并促使两种蛋白质形成额外的 α 螺旋区域。
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引用次数: 0
In Silico Study of Solvation Effects in Solutions of Biomolecules: Possibilities of an Approach Based on the 3D-Distribution of Solvent Atomic Density 生物大分子溶液溶解效应的硅学研究:基于溶剂原子密度三维分布的方法的可能性
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-07 DOI: 10.1134/s0006350923050123
S. E. Kruchinin, M. V. Fedotova, E. E. Kislinskaya, G. N. Chuev

Abstract

Biomolecular solvation plays a key role in nature. Biological activity and target functions of molecules depend on the features of the process. However, hydration of biomolecules is an intricate problem in both experimental research and computer simulations. The possibilities of the non-empirical 3D-SDFT/3D-RISM approach based on the 3D-distribution of the solvent atomic density to study the features of biomolecule hydration were demonstrated with examples of a number of amino acids (Gly-ZW, L-Ala-ZW, L-Val-ZW, and L-Pro-ZW), two model proteins (bovine pancreatic trypsin inhibitor (BPTI)) and protein tyrosine phosphatase 1B (PTP1B)), and PTP1B complexes with inhibitors. The results showed that using this approach it is possible to simultaneously obtain a detailed and holistic description of the hydration shell structure of biomolecules.

摘要 生物分子溶解在自然界中发挥着关键作用。分子的生物活性和目标功能取决于这一过程的特征。然而,无论是在实验研究还是计算机模拟中,生物分子的水合作用都是一个错综复杂的问题。我们以一些氨基酸(Gly-ZW、L-Ala-ZW、L-Val-ZW 和 L-Pro-ZW)、两种模型蛋白质(牛胰蛋白酶抑制剂 (BPTI) 和蛋白酪氨酸磷酸酶 1B (PTP1B))以及 PTP1B 与抑制剂的复合物为例,展示了基于溶剂原子密度三维分布的非经验三维-SDFT/三维-RISM 方法研究生物大分子水合特征的可能性。结果表明,使用这种方法可以同时获得生物大分子水合壳结构的详细和整体描述。
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引用次数: 0
Mechanism of Action of the Low-Frequency Electromagnetic Field on Aqueous Solutions of Biopolymers 低频电磁场对生物聚合物水溶液的作用机制
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-07 DOI: 10.1134/s0006350923050299
E. E. Tekutskaya, G. P. Ilchenko, M. G. Baryshev

Abstract

This paper presents the transformation mechanism of a signal from the magnetic component of a low-frequency electromagnetic field with extremely low energy into a chemical and biochemical response in aqueous solutions of nucleic acids and proteins. The developed theoretical model shows that oxidative DNA damage and conformational transitions in proteins are based on a universal mechanism for changing the amount of the most long-lived form, hydrogen peroxide, in a chemical oscillator of mutual transformations of reactive oxygen species under a low-intensity electromagnetic field. It has been experimentally found that the content of hydrogen peroxide in solutions of biopolymers resonantly depends on the frequency of the applied field. Conformational changes in proteins are accompanied by increasing accessibility and activity of the nucleophilic centers, which are potential targets for reactive oxygen species. Complete unfolding and denaturation of the protein amino-acid chain in a low-frequency electromagnetic field did not occur. It has been shown that the enhanced formation of hydrogen peroxide at 3 and 50 Hz leads to oxidative modification of nitrogenous bases in DNA.

摘要 本文介绍了能量极低的低频电磁场磁分量信号在核酸和蛋白质水溶液中转化为化学和生化反应的机制。所建立的理论模型表明,在低强度电磁场下,活性氧相互转化的化学振荡器中,DNA 的氧化损伤和蛋白质的构象转变是基于一种改变最长寿形式--过氧化氢--数量的普遍机制。实验发现,生物聚合物溶液中过氧化氢的含量与应用场的频率有共振关系。蛋白质的构象变化伴随着亲核中心的可及性和活性的增加,而亲核中心是活性氧的潜在目标。在低频电磁场中,蛋白质氨基酸链不会完全展开和变性。研究表明,在 3 赫兹和 50 赫兹频率下,过氧化氢的形成增强,导致 DNA 中的含氮碱基发生氧化修饰。
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引用次数: 0
Evaluation of the Efficiency of Intersystem Crossing to a Triplet State of Fullerene in Complexes with Amino Acids 评估富勒烯与氨基酸复合物的三重态系统间交叉效率
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-07 DOI: 10.1134/s000635092305007x
A. S. Buchelnikov, P. A. Sokolov, R. R. Ramasanoff

Abstract

The important photophysical process that determines the efficiency of photosensitizers is saturation of the triplet state through the intersystem crossing during light absorption. We studied the C60 fullerene complexes with the amino acids (glycine, lysine, methionine, and threonine) as promising photosensitizers. The calculations for all these complexes demonstrate high values of the transition rate constants to the triplet states and a high probability of generating reactive oxygen species upon excitation in visible light. The carboxyl groups of amino acids, which are not involved in electronic excitation, can be used to conjugate photoactive complexes with a tumor-targeting drug delivery system, such as specific DNA aptamers.

摘要 决定光敏剂效率的重要光物理过程是在光吸收过程中通过系统间交叉使三重态饱和。我们研究了 C60 富勒烯与氨基酸(甘氨酸、赖氨酸、蛋氨酸和苏氨酸)的配合物,它们是很有前途的光敏剂。对所有这些复合物的计算都表明,它们向三重态转变的速率常数很高,在可见光下激发时产生活性氧的概率也很高。氨基酸的羧基不参与电子激发,可用于将光敏复合物与肿瘤靶向药物输送系统(如特异性 DNA aptamers)结合在一起。
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引用次数: 0
Conformational Features of Beta-Amyloid Peptide 25–35 β-淀粉样肽 25-35 的构象特征
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-07 DOI: 10.1134/s0006350923050020
G. A. Agaeva, G. Z. Najafova

Abstract

Beta-amyloid peptide (Aβ) plays an important role in the mechanism of neurodegeneration in Alzheimer’s disease. A fragment of beta-Aβ(25–35) amyloid peptide with the sequence GSNKGAIIGLM is considered to be the functional domain of the amyloid Aβ peptide responsible for its neurotoxic properties and the biologically active Aβ region. Conformational analysis by the method of molecular mechanics of each peptide segment of the C-terminal part of the peptide revealed a limited number of the most probable conformations and clearly defined the forces stabilizing the structures. The results we obtained showed that the Aβ(25–35) peptide energetically preferentially adopts the a-helical conformation at the C-terminal octapeptide segment. The molecular dynamics method was used to model the intramolecular mobility pattern of the Aβ(25–35) peptide molecule. It is shown that in the low-energy conformations of the Aβ(25–35) peptide, the flexible structures in its N-terminal region were oriented differently with respect to the structures in the C-terminal part.

摘要β-淀粉样肽(Aβ)在阿尔茨海默病的神经变性机制中起着重要作用。序列为 GSNKGAIIGLM 的 beta-Aβ(25-35)淀粉样肽片段被认为是淀粉样 Aβ 肽的功能域,负责其神经毒性特性和具有生物活性的 Aβ 区域。通过分子力学方法对肽 C 端部分的每个肽段进行构象分析,发现了数量有限的最可能构象,并明确了稳定结构的作用力。我们获得的结果表明,Aβ(25-35)肽在能量上优先采用 C 端八肽段的 a 型螺旋构象。分子动力学方法用于模拟 Aβ(25-35)肽分子的分子内流动模式。结果表明,在 Aβ(25-35)肽的低能构象中,其 N 端区域的柔性结构与 C 端部分的结构方向不同。
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引用次数: 0
Inhalation of High Doses of Gaseous Nitric Oxide in HIV Infection 在艾滋病毒感染中吸入高剂量的一氧化氮气体
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-07 DOI: 10.1134/s0006350923050196
A. V. Pekshev, A. B. Vagapov, N. A. Sharapov, A. F. Vanin

Abstract

The therapeutic effect of high-dose inhalation of nitrogen oxide gas (at a NO concentration of at least 1000 ppm) in two HIV-infected patients was demonstrated. Inhaled NO therapy led to a rapid decrease in viral load to an undetectable level, which persisted even after the period of analytical interruption of treatment. It was assumed that the relief of HIV infection was due to nitrosonium cations NO+ formed in the blood from neutral NO molecules. The subsequent conversion of NO+ cations in their reaction with hydroxyl anions into nitrite anions was prevented by the binding of NO+ cations with chlorine anions and the formation of nitrosochloride in the blood. The entry of this agent from the blood into cells and tissues provided the transfer of NO+ cations into them. The interaction of nitrosochloride with thiols could lead to the appearance of corresponding S-nitrosothiols in cells and tissues as NO donors.

摘要 在两名艾滋病毒感染者身上证实了大剂量吸入氧化氮气体(氧化氮浓度至少为 1000 ppm)的治疗效果。吸入氮氧化物疗法使病毒载量迅速下降到检测不到的水平,甚至在分析性中断治疗后仍能持续。据推测,艾滋病毒感染的缓解是由于中性 NO 分子在血液中形成了亚硝鎓阳离子 NO+。随后,NO+阳离子与羟基阴离子反应转化为亚硝酸阴离子,NO+阳离子与氯阴离子结合并在血液中形成亚硝基盐酸盐,从而阻止了亚硝酸阴离子的转化。这种物质从血液进入细胞和组织后,可将 NO+ 阳离子转移到细胞和组织中。亚硝基盐酸盐与硫醇的相互作用可导致细胞和组织中出现相应的 S-亚硝基硫醇,成为一氧化氮的供体。
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引用次数: 0
The Composition and Mitogenic Activity of Polysaccharide from Solanum tuberosum L. 茄科植物多糖的成分和有丝分裂活性
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-07 DOI: 10.1134/s0006350923050093
E. A. Generalov, L. V. Yakovenko

Abstract

The STP polysaccharide was isolated from an aqueous extract of Solanum tuberosum L. and purified by ion exchange chromatography and gel filtration. Its molecular mass was determined by gel-penetrating chromatography and high-performance liquid chromatography, and its monosaccharide composition was analyzed by high-performance liquid chromatography and gas chromatography using a flame ionization detector and a capillary column. It was shown that STP polysaccharide consists of galactose and arabinose at 37.5% and 23.5%, respectively, as well as uronic acids (9.7%), glucose monosaccharide residues (15%), and proteins (at least 9%). The molecular mass of STP is 70 kDa. The method of IR-Fourier spectroscopy was used for the structural analysis of STP. The mitogenic activity of the extracted polysaccharide was comparable to the activity of lipopolysaccharide.

摘要 从茄科植物Solanum tuberosum L.的水提取物中分离出STP多糖,并通过离子交换色谱和凝胶过滤进行纯化。用凝胶穿透色谱法和高效液相色谱法测定了其分子质量,并用高效液相色谱法和气相色谱法(火焰离子化检测器和毛细管柱)分析了其单糖组成。结果表明,STP 多糖由半乳糖和阿拉伯糖组成,分别占 37.5%和 23.5%,此外还有尿酸(9.7%)、葡萄糖单糖残基(15%)和蛋白质(至少 9%)。STP 的分子质量为 70 kDa。红外-傅里叶光谱法用于分析 STP 的结构。提取多糖的有丝分裂活性与脂多糖的活性相当。
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引用次数: 0
Refinement of Nucleosome Positions within Individual Genes Using Molecular Modeling Methods and MNase Sequencing Data 利用分子建模方法和 MNase 测序数据完善单个基因内的核小体位置
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-07 DOI: 10.1134/s0006350923050317
V. A. Vasilev, D. M. Ryabov, A. K. Shaytan, G. A. Armeev

Abstract

Chromatin organization plays an important role in regulating the genetic machinery of the cell. A nucleosome is a basic unit of chromatin packaging and harbors about 145 bp of DNA. The packaging of genetic material and its accessibility to transcription enzymes and other regulatory chromatin proteins depend on the positions of nucleosomes. MNase sequencing is used to examine the nucleosome positions in a genome. MNase sequencing data are sufficient for detecting the presence of nucleosomes on a sequence, but their precise locations can be problematic to establish. Additional data filtering and processing are required for accurate determination of nucleosome positions. A combined method was developed using a geometric analysis of the molecular models of nucleosome chains to select the possible nucleosome positions on the basis of MNase sequencing data. The algorithm efficiently eliminates the inaccessible nucleosome chain combinations and conformationally prohibited nucleosome positions.

摘要 染色质组织在调节细胞遗传机制方面发挥着重要作用。核小体是染色质包装的基本单位,容纳约 145 bp 的 DNA。遗传物质的包装及其对转录酶和其他染色质调控蛋白的可及性取决于核小体的位置。MNase 测序用于检测基因组中核小体的位置。MNase 测序数据足以检测序列中核小体的存在,但要确定核小体的精确位置却很困难。要准确确定核小体的位置,还需要额外的数据过滤和处理。通过对核小体链的分子模型进行几何分析,开发出了一种综合方法,可根据 MNase 测序数据选择可能的核小体位置。该算法有效地排除了无法进入的核糖体链组合和构象禁用的核糖体位置。
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引用次数: 0
Structural and Functional Assessment of the Condition of the Wound Bed by Microwave Dielectrometry and Laser Doppler Flowmetry 用微波介电测量法和激光多普勒血流测量法评估伤口床的结构和功能状况
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-07 DOI: 10.1134/s0006350923050160
A. K. Martusevich, A. V. Surovegina, V. V. Nazarov, A. S. Fedotova

Abstract

The aim of the work was to develop and test a combined method to assess the structural and functional features of a burn wound and periwound area with the use of microwave dielectrometry and Doppler flowmetry. The study included 20 Wistar rats used to model a contact thermal injury and 10 intact rats. The wound condition was assessed 24 and 72 hours after burn injury. The dielectric properties of tissues were studied using a hardware and software complex for microwave (MW) resonant near-field probing. A sharp coordinated decrease in microcirculation intensity and dielectric permittivity was observed in wound tissues in the early post-injury period (day 1 after injury). The parameters gradually and partially restored by the end of day 3 after burning. A compensatory increase in microcirculatory blood flow was detected in the periwound area, leading to a higher degree of tissue hydration and, consequently, higher values of the two parameters. A regulatory imbalance of factors that ensure the capillary blood flow in the wound area and surrounding tissues was found to develop after a thermal injury. The imbalance was compensatory in nature and contributed to the inhibition of regeneration processes in the absence of adequate correction. Thus, a combination of the two methods used in the study may potentially provide more specific information in order to describe the structural and functional features of a tissue of interest and their dynamics, as was demonstrated with the example of an experimental burn wound.

摘要 这项工作旨在开发和测试一种综合方法,利用微波介电测量法和多普勒血流测量法评估烧伤创面和创面周围的结构和功能特征。研究对象包括 20 只用于模拟接触性热损伤的 Wistar 大鼠和 10 只完好无损的大鼠。烧伤后 24 小时和 72 小时对伤口状况进行评估。使用微波(MW)共振近场探测的软硬件组合研究了组织的介电特性。在伤后早期(伤后第 1 天)观察到伤口组织的微循环强度和介电介电常数急剧下降。到烧伤后第 3 天结束时,这些参数逐渐部分恢复。在伤口周围区域检测到微循环血流的代偿性增加,导致组织水化程度提高,从而使这两个参数值升高。热损伤后,确保伤口区域和周围组织毛细血管血流的各种因素出现了调节失衡。这种失衡具有代偿性质,在没有得到适当纠正的情况下会抑制再生过程。因此,将研究中使用的两种方法结合起来,有可能提供更具体的信息,以描述相关组织的结构和功能特征及其动态变化,这一点已在实验性烧伤创面中得到证实。
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引用次数: 0
Proteostasis of Heat Shock Protein HSP90 in Skeletal Muscles of the Long-Tailed Ground Squirrel during Hibernation 冬眠期间长尾地松鼠骨骼肌中热休克蛋白 HSP90 的蛋白稳态
IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-03-07 DOI: 10.1134/s000635092305010x
Yu. V. Gritsyna, S. S. Popova, G. Z. Mikhailova, L. G. Bobyleva, S. N. Udaltsov, O. S. Morenkov, N. M. Zakharova, I. M. Vikhlyantsev

Abstract

Changes in the content of heat shock protein 90 (HSP90) in m. soleus (contains mainly fibers expressing the “slow” isoform I MyHC) and m. gastrocnemius (contains mainly fibers expressing the “fast” isoforms II MyHC) of a true hibernant, the long-tailed ground squirrel (Urocitellus undulatus), during different periods of the annual cycle, summer activity (seasonal control), hypothermia/winter torpor, and winter (interbout) activity, were studied. It was found that despite the development of atrophic changes that were more pronounced in the “fast” m. gastrocnemius, the content of HSP90 in both muscles did not change throughout the hibernation period. The role of HSP90 in maintaining the stability of the titin giant sarcomeric protein molecules during the periods of the animal’s entry into and exit from hypothermia, when the activity of calpain proteases increased due to the increased content of Ca2+ in the cytosol of muscle cells, as well as during hypothermia, when the activity of calpains most likely was not completely inhibited, was discussed. During the winter/interbout activity, when there was an increased titin turnover in the striated ground squirrel muscles, a constant content of HSP90 was apparently necessary for the correct folding of newly synthesized titin molecules and their embedding into sarcomeres, as well as for the removal of improperly folded and old titin molecules/fragments, as well as other proteins. Thus, HSP90 proteostasis in skeletal muscles of the long-tailed ground squirrel could contribute to maintaining a stable level of titin and, possibly, other sarcomeric proteins during hibernation, which, in turn, would contribute to maintaining a highly ordered sarcomeric structure and the necessary level of contractile muscle activity in different phases of the hibernation–wakefulness cycle.

摘要真正冬眠的长尾地松鼠(Urocitellus undulatus)的比目鱼肌(主要含有表达 "慢 "异构体I MyHC的纤维)和腓肠肌(主要含有表达 "快 "异构体II MyHC的纤维)中热休克蛋白90(HSP90)含量的变化。研究了真正冬眠的长尾地松鼠(Urocitellus undulatus)在年周期的不同时期(夏季活动(季节控制)、低温/冬季冬眠和冬季(间歇期)活动)中比目鱼肌(主要含有表达 "慢 "异构体 I MyHC 的纤维)和腓肠肌(主要含有表达 "快 "异构体 II MyHC 的纤维)中热休克蛋白 90(HSP90)含量的变化。研究发现,尽管腓肠肌的萎缩性变化在 "快速 "腓肠肌中更为明显,但两块肌肉中的 HSP90 含量在整个冬眠期都没有变化。在动物进入低体温期和脱离低体温期,钙蛋白酶的活性会因肌肉细胞胞质中 Ca2+ 含量的增加而增加,而在低体温期,钙蛋白酶的活性很可能没有被完全抑制,因此讨论了 HSP90 在维持 titin 巨型肉瘤蛋白分子稳定性方面的作用。在冬季/冬季活动期间,横纹肌中的钛蛋白更替增加,HSP90的恒定含量显然是新合成的钛蛋白分子正确折叠和嵌入肌节,以及清除折叠不当和老化的钛蛋白分子/碎片及其他蛋白质所必需的。因此,长尾地松鼠骨骼肌中的HSP90蛋白稳态可能有助于在冬眠期间维持稳定水平的钛蛋白以及其他肉瘤蛋白,这反过来又有助于在冬眠-觉醒周期的不同阶段维持高度有序的肉瘤结构和必要水平的收缩肌活动。
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引用次数: 0
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